The anticoagulation therapy has been extensively performed for the prevention and treatment of thromboembolic diseases caused by blood hypercoagulability, and drugs such as heparin and warfarin potassium have been frequently used as anticoagulant agents at present.
However, heparin shows inhibitory activity on thrombin and activated blood coagulation factor X, and has been known to have a risk of causing bleeding tendency.
Warfarin potassium is an anticoagulant which controls biosynthesis of vitamin K-dependent coagulation factor, and it is difficult to control the anticoagulation capacity due to its action mechanism when this drug is used in the prevention and treatment of thromboembolic diseases. Therefore, this drug is extremely hard to use clinically.
In recent years, selective thrombin inhibitors have been developed and have been used clinically. However, since thrombin plays a close part in the conversion of fibrinogen into fibrin in blood coagulation cascade reactions and platelet activation and aggregation, the thrombin inhibitors have similar disadvantages to heparin on the point of view of the safety such as bleeding tendency. Moreover, it has been reported that their efficacies are not necessarily sufficient.
On the other hand, activated blood coagulation factor X, which acts at the juncture of the extrinsic and intrinsic blood coagulation cascade reactions, located on the upstream of thrombin, so that an anticoagulation activity of activated blood coagulation factor X is more efficient than that of thrombin inhibitors. Therefore, activated blood coagulation factor X inhibitors attract public attentions as drugs having a possibility to inhibit the coagulation system effectively.
Furthermore, with the changing into European and American life styles and the aging of population have been developed in recent years, incidences of thromboembolic diseases such as myocardial infarction and arteriovenous obstruction will go on increasing, and therefore, the social importance of more efficient anticoagulants has been going on increasing, and the demands on development of such anticoagulants are great.